A Randomized, Double-Blinded, Placebo-Controlled Trial of a Dipeptidyl Peptidase-4 Inhibitor (Sitagliptin, Januvia) for Reducing Inflammation and Immune Activation in HIV-Infected Men and Women: A Multicenter Trial of the AIDS Clinical Trials Group (ACTG)
The purpose of the study is to evaluate whether sitagliptin (Januvia is the brand name for sitagliptin) reduces inflammation and immune activation markers in HIV-infected men and women when compared to a placebo (inactive medication like a dummy pill). The study evaluated whether taking 100 mg of sitagliptin by mouth daily for 16 weeks is safe and effective for HIV-infected persons on antiretroviral therapy (ART) who do not have diabetes. Sitagliptin is a medication that is used to treat people with diabetes (high blood sugar) but also may reduce inflammation in the body.
• Documented HIV-1 infection.
• Currently on an antiretroviral regimen consisting of at least 2 NRTIs and either a protease inhibitor boosted with low dose ritonavir, an integrase inhibitor, or an NNRTI. (Other ART regimens may be acceptable. Sites must consult the protocol team for approval)
• Currently on continuous ART for ≥48 weeks prior to study entry with no interruption longer than 7 consecutive days during that period.
• Plasma HIV-1 RNA levels below 75 copies/mL for at least 48 weeks prior to study entry. The participant must have a minimum of two values in the last 48 weeks obtained \>30 days apart, with the most recent value obtained within 90 days prior to entry. (Single determinations that are between the assay quantification limit and 500 copies/mL (i.e., blips) are allowed as long as the preceding and subsequent determinations are below the level of quantification).
• CD4+ cell count ≥100 cells/mm\^3 obtained within 90 days prior to study entry.
• The following laboratory values obtained within 90 days prior to entry.
‣ Absolute neutrophil count (ANC) ≥750/mm\^3
⁃ Hemoglobin ≥8.0 g/dL
⁃ Platelet count ≥50,000/mm\^3
⁃ Calculated creatinine clearance (CrCl) ≥60 mL/min as estimated by the Cockroft-Gault formula NOTE: Calculation for the Cockcroft-Gault equation is available at https://www.fstrf.org/apps/cfmx/apps/common/Portal/index.cfm
⁃ Aspartate aminotransferase (AST) (SGOT) ≤5 x upper limit of normal (ULN).
⁃ alanine aminotransferase (ALT) (SGPT) ≤5 x ULN.
⁃ alkaline phosphatase ≤5 x ULN.
⁃ Total bilirubin ≤2.5 x ULN (if the participant is receiving atazanavir, a total bilirubin of ≤5 x ULN is acceptable).
⁃ Hemoglobin A1C ≤6.5%
• For females of reproductive potential, adequate contraception.
• Karnofsky performance score ≥70 within 90 days prior to entry.
• Ability and willingness of participant or legal guardian/representative to provide informed consent.
• Participants on statin therapy must be stable on the same dose for at least the prior 12 weeks with no anticipated change in statin or dose during the intervention.